Summary: Dr. Marin-Castaño’s research program uses tissue culture techniques and experimental models combining molecular, cellular, genetic, biochemical, and physiologic assays to investigate the pathogenesis of Age-Related Macular Degeneration.

Maria E. Marin-Castaño, M.D, Ph.D.
Research Assistant Professor

View published research articles by this doctor in the National Library of Medicine.

Current Research Summary: Age-Related Macular Degeneration is a late onset (after age 50), progressive degeneration of the retina associated with vision loss coupled with a spectrum of specific clinical, physiological and histopathological features. ARMD affects 30% of people older than age 70, and is the leading cause of blindness in the elderly. Fourteen million people may be affected in the United States and over one million in Florida. Loss or dysfunction of retinal photoreceptors is the ultimate cause of vision loss. However, the initial pathogenic target of ARMD is the retinal pigment epithelium (RPE), Bruch’s membrane (BrM), and the choriocapillaris (CC). Early ARMD (“atrophic” or “dry” degeneration) can be conceptualized as a disorder of the extracellular matrix (ECM), characterized by progressive thickening and by accumulation of various lipid rich extracellular matrix (ECM) deposits under the RPE. Abnormal ECM production or turnover likely contributes to the pathology of the ARMD. Current therapies are not effective, so an important focus is prevention of risk factors. The major risk factors for the development of ARMD are systemic arterial hypertension and environmental toxins. However, the mechanisms involved have not been elucidated.

Dr. Marin-Castaño’s research is directed at discovering the etiologies of subRPE deposits formation. The focus is on the RPE and on a specific type of cellular repair called “blebbing,” which we propose as a major causal mechanism in ARMD. An important feature of this hypothesis is the interaction between oxidant injury stimuli and regulating cofactors. Oxidant injury stimuli refers to a group of environmental toxins which can induce cell membrane “blebs” (Blebs are formed when the plasma membrane detaches from the cortical actin layer by an unknown mechanism) formation and accumulation under the RPE as basal laminar deposits (BLD). Subsequent RPE upregulated release or synthesis of metalloproteinases (MMPs), collagens, and other molecules responsible for basement membrane and BrM turnover, stimulated by cofactors such as mediators related to hypertension leading to admixture of blebs into BrM and formation of new basement membrane under the RPE.

Results indicate at least three families of injury stimuli can induce injure to cell membrane: 1) soluble oxidants, 2) extracellular oxidants, and 3) mitochondria toxins.

The current focus of the lab involves effects of hydroquinone (HQ), an oxidant environmental risk factor (which, interacts with mitochondrial oxidases, leading to leakage of superoxide into the cytoplasm), and mediators (i.e., angiotensin and endothelin) involved in regulation of hypertension in tissue culture and experimental models. These and other possible candidates are being studies more extensively in our lab.

Using a combination of different techniques such as zymography, Western blotting, collagen accumulation, immunohistochemical, and transmission electron microscopy(TEM), Dr. Marin-Castaño’s group has discovered a strong association between HQ and subRPE deposits formation in vitro and in vivo. In human RPE cells, nonlethal HQ induce blebbing, actin filament aggregation, and diminution of ECM turnover favoring deposit accumulation thickening of BrM. In an experimental mouse model for dry AMD, oral HQ induces basal laminar deposits.

Other ongoing work involves the investigation of the effects of hypertension alone or in combination with HQ on the severity and progression of subRPE deposits in both tissue culture and experimental model for renovascular hypertension.

Our long term goal is to elucidate the mechanism and regulation of oxidant induced blebbing and to understand the factors that control excessive blebbing in order to suggest new directions for treatment of early ARMD and to develop blood test to ascertain individual prognosis for progression.